Luminescence-based Imaging Approaches in the Field of Interventional Molecular Imaging

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Editorial: state-of-the-art fluorescence image-guided surgery: current and future developments

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Non-covalent (iso)guanosine-based ionophores for alkali(ne earth) cations

Different (iso)guanosine-based self-assembled ionophores give distinctly different results in extraction experiments with alkali(ne earth) cations. A lipophilic guanosine derivative gives good extraction results for K+, Rb+, Ca2+, Sr2+, and Ba2+ and in competition experiments it clearly favors the divalent Sr2+ (and Ba2+) cations. 1,3-Alternate calix[4]arene tetraguanosine hardly shows any improvement in the extraction percentages compared to its reference compound 1,3-alternate calix[4]arene tetraamide. This indicates that one G-quartet does not provide efficient cation complexation under these conditions. In the case of the lipophilic isoguanosine derivative there is a cation size dependent affinity for the monovalent cations (Cs+ Rb+ K+), but not for the divalent cations (Ca2+ > Ba2+ > Sr2+ > Mg2+). In competition experiments the isoguanosine derivative, unlike guanosine, does not discriminate between monovalent and divalent cations, giving an almost equal extraction of Cs+ and Ba2+.\ud \u

How molecular imaging will enable robotic precision surgery: the role of artificial intelligence, augmented reality, and navigation

Molecular imaging is one of the pillars of precision surgery. Its applications range from early diagnostics to therapy planning, execution, and the accurate assessment of outcomes. In particular, molecular imaging solutions are in high demand in minimally invasive surgical strategies, such as the substantially increasing field of robotic surgery. This review aims at connecting the molecular imaging and nuclear medicine community to the rapidly expanding armory of surgical medical devices. Such devices entail technologies ranging from artificial intelligence and computer-aided visualization technologies (software) to innovative molecular imaging modalities and surgical navigation (hardware). We discuss technologies based on their role at different steps of the surgical workflow, i.e., from surgical decision and planning, over to target localization and excision guidance, all the way to (back table) surgical verification. This provides a glimpse of how innovations from the technology fields can realize an exciting future for the molecular imaging and surgery communities.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Dendrimer-encapsulated nanoparticle-core micelles as a modular strategy for particle-in-a-box-in-a-box nanostructures

The hierarchically controlled synthesis and characterization of self-assembling macromolecules and particles are key to explore and exploit new nanomaterials. Here we present a versatile strategy for constructing particle-in-a-box-in-a-box systems by assembling dendrimer-encapsulated gold nanoparticles (DENs) into dendrimicelles. This is realized by combining positively charged PAMAM dendrimers with a negative-neutral block copolymer. The number of particles per dendrimicelle can be controlled by mixing DENs with empty PAMAM dendrimers. The dendrimicelles are stable in solution for months and provide improved resistance for the nanoparticles against degradation. The dendrimicelle strategy provides a flexible platform with a plethora of options for variation in the type of nanoparticles, dendrimers and block copolymers used, and hence is tunable for applications ranging from nanomedicine to catalysis.</p

The influence of systematic structure alterations on the photophysical properties and conjugation characteristics of asymmetric cyanine 5 dyes

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Multicompartment dendrimicelles with binary, ternary and quaternary core composition

Hierarchically built-up multicompartment nanoaggregate systems are of interest for, e.g., novel materials and medicine. Here we present a versatile strategy to generate and unambiguously characterize complex coacervate-core micelles by exploiting four different dendrimeric subcomponents as core-units. The resulting mesoscale structures have a hydrodynamic diameter of 50 nm and a core size of 33 nm, and host about thirty 6th generation polyamidoamine (PAMAM) dendrimers. We have used FRET (efficiency of similar to 0.2) between fluorescein and rhodamine moieties immobilized on separate PAMAM dendrimers (G6-F and G6-R, respectively) to prove synchronous encapsulation in the micelle core. Tuning the proximity of the FRET pair molecules either by varying the G6-F : G6-R ratio, or by co-assembling non-functionalized dendrimer (G6-E) in the core, reveals the optimal FRET efficiency to occur at a minimum of 70% loading with G6-F and G6-R. Additional co-encapsulation of 6th generation gold dendrimer-encapsulated nanoparticles (G6-Au) in the micelle core shows a dramatic reduction of the FRET efficiency, which can be restored by chemical etching of the gold nanoparticles from within the micellar core with thiols, leaving the micelle itself intact. This study reveals the controlled co-assembly of up to four different types of subcomponents in one single micellar core and concomitantly shows the wide variety of structures that can be made with a well-defined basic set of subcomponents. It is straightforward to design related strategies, to incorporate inside one micellar core, e.g., even more than 4 different dendrimers, or other classes of (macro)molecules, with different functional groups, other FRET pairs or different encapsulated metal nanoparticles.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Development and prospects of dedicated tracers for the molecular imaging of bacterial infections

Bacterial infections have always been, and still are, a major global healthcare problem. For accurate treatment it is of utmost importance that the location(s), severity, type of bacteria, and therapeutic response can be accurately staged. Similar to the recent successes in oncology, tracers specific for molecular imaging of the disease may help advance the patient management. Chemical design and bacterial targeting mechanisms are the basis for the specificity of such tracers. The aim of this review is to provide a comprehensive overview of the molecular imaging tracers developed for optical and nuclear identification of bacteria and bacterial infections. Hereby we envision that such tracers can be used to diagnose infections and aid their clinical management. From these compounds we have set-out to identify promising targeting mechanisms and select the most promising candidates for further development.The Netherlands Organisation for Scientific Research (NWO; STW BGT 11272).http://pubs.acs.org/bchb201

A DROP-IN gamma probe for robot-assisted radioguided surgery of lymph nodes during radical prostatectomy

Background: The DROP-IN gamma probe was introduced to overcome the restricted manoeuvrability of traditional laparoscopic gamma probes. Through enhanced manoeuvrability and surgical autonomy, the DROP-IN promotes the implementation of radioguided surgery in the robotic setting.Objective: To confirm the utility and safety profile of the DROP-IN gamma probe and to perform a comparison with the traditional laparoscopic gamma probe and fluorescence guidance.Design, setting, and participants: Twenty-five prostate cancer patients were scheduled for a robot-assisted sentinel lymph node (SN) procedure, extended pelvic lymph node dissection, and prostatectomy at a single European centre.Surgical procedure: After intraprostatic injection of indocyanine green (ICG)-Tc-99m-nanocolloid (n = 12) or Tc-99m-nanocolloid + ICG (n = 13), SN locations were defined using preoperative imaging. Surgical excision of SNs was performed under image guidance using the DROP-IN gamma probe, the traditional laparoscopic gamma probe, and fluorescence imaging.Measurements: Intraoperative SN detection was assessed for the different modalities and related to anatomical locations. Patient follow-up was included (a median of 18 mo).Results and limitations: Overall, 47 SNs were pursued in vivo by the DROP-IN gamma probe, of which 100% were identified. No adverse events related to its use were observed. In vivo fluorescence imaging identified 91% of these SNs. The laparoscopic gamma probe identified only 76% of these SNs, where the detection inaccuracies appeared to be related to specific anatomical regions.Conclusions: Owing to improved manoeuvrability, the DROP-IN probe yielded improved SN detection rates compared with the traditional gamma probe and fluorescence imaging. These findings underline that the DROP-IN technology provides a valuable tool for radioguided surgery in the robotic setting.Patient summary: Radioguided robot-assisted surgery with the novel DROP-IN gamma probe is feasible and safe. It enables more efficient intraoperative identification of sentinel lymph nodes than can be achieved with a traditional laparoscopic gamma probe. The use of the DROP-IN probe in combination with fluorescence imaging allows for a complementary optical confirmation of node localisations. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology.Oncologic Imagin

Fluorescence background quenching as a means to increase Signal to Background ratio - a proof of concept during Nerve Imaging

Introduction: Adequate signal to background ratios are critical for the implementation of fluorescence-guided surgery technologies. While local tracer administrations help to reduce the chance of systemic side effects, reduced spatial migration and non-specific tracer diffusion can impair the discrimination between the tissue of interest and the background. To combat background signals associated with local tracer administration, we explored a pretargeting concept aimed at quenching non-specific fluorescence signals. The efficacy of this concept was evaluated in an in vivo neuronal tracing set-up.Methods: Neuronal tracing was achieved using a wheat germ agglutinin (WGA) lectin. functionalized with an azide-containing Cy5 dye (N-3-Cy5-WGA). A Cy7 quencher dye (Cy7-DBCO) was subsequently used to yield Cy7-Cy5-WGA, a compound wherein the Cy5 emission is quenched by Forster resonance energy transfer to Cy7. The photophysical properties of N-3-Cy5-WGA and Cy7-Cy5-WGA were evaluated together with deactivation kinetics in situ, in vitro (Schwannoma cell culture), ex vivo (muscle tissue from mice; used for dose optimization), and in vivo (nervus ischiadicus in THY-1 YFP mice).Results: In situ, conjugation of Cy7-DBCO to N-3-Cy5-WGA resulted in >90% reduction of the Cy5 fluorescence signal intensity at 30 minutes after addition of the quencher. In cells, pretargeting with the N-3-Cy5-WGA lectin yielded membranous staining, which could efficiently be deactivated by Cy7-DBCO over the course of 30 minutes (91% Cy5 signal decrease). In ex vivo muscle tissue, administration of Cy7-DBCO at the site where N-3-Cy5-WGA was injected induced 80-90% quenching of the Cy5-related signal after 10-20 minutes, while the Cy7-related signal remained stable over time. In vivo, Cy7-DBCO effectively quenched the non-specific background signal up to 73% within 5 minutes, resulting in a 50% increase in the signal-to-background ratio between the nerve and injection site.Conclusion: The presented pretargeted fluorescence-quenching technology allowed fast and effective reduction of the background signal at the injection site, while preserving in vivo nerve visualization. While this proof-of-principle study was focused on imaging of nerves using a fluorescent WGA-lectin, the same concept could in the future also apply to applications such as sentinel node imaging